Apoptosis, or programmed cell death is a fundamentally biological process that is required to maintain the integrity and homeostasis of multicellular organism. Inappropriate apoptosis has been associated with many of the most intractable of human diseases, including neurodegenerative disorders and cancer. In an age-related conditions, such as Alzheimer's disease and stroke, there is an increase in an neuronal cell death. A cascade of gene expression is essential to effect neuronal apoptosis. The transcription factor c-Jun is one of the earliest and most consistent marker for neurons that response to neuronal injury and neurodegenerative disorders. Overexpression of c- Jun can trigger apoptosis in sympathetic neurons. Antagonization of c- Jun activity by overexpression of transactivation-defective c-Jun mutants prevents them against nerve growth factor (NGF) withdrawal- induced death. It appears that c-Jun might cause neuronal cell death by initiating the transcription of downstream target genes whose gene products are executors or triggers of the cell death program. However, c-Jun downstream target gene(s) that effect neural apoptosis are largely unknown. The primary goal of this proposal is to directed toward identifying Jun target genes and toward dissecting the mechanism by which is c-Jun is triggering apoptosis.